Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina

Abstract

High acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible model organisms lack a fovea, its specialized function and dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate and validate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >65 cell types match between the two regions, but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved, but that projection neuron types and programs diverge, despite conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 6 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species. $00&;789: 4789:

Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution

“…The cell-type transcriptome atlas of developed organoids and adult human retinas allows mapping of disease-associated genes to particular cell types. Single-cell transcriptome atlases for mouse (Macosko et al, 2015;Shekhar et al, 2016) and non-human primate neural retinas (Peng et al, 2019), as well as several hours post mortem human neural retinas, pigment epithelium, and choroid (Kim et al, 2019;Liang et al, 2019;Lukowski et al, 2019;Menon et al, 2019;Peng et al, 2019;Voigt et al, 2019), have been reported. The human atlas from functionally intact, 5-min post mortem neural retinas and from retinal pigment epithelium and choroid described here provides definitive information linking diseases to human cell types.…”

An Annotated Journey through Modern Visual Neuroscience

“…It is inevitable, though, in putting together a classic reading list that many foundational studies will be left out. We regret that the list did not include work related to many topics, including but not restricted to, functional connectivity (Gilbert and Wiesel, 1989), color processing (Livingstone and Hubel, 1984), binocular or stereo vision (Barlow et al, 1967), attention (Cohen and Maunsell, 2009), eye movements (Wurtz and Goldberg, 1972;Schiller and Stryker, 1972), predictive coding (Rao and Ballard, 1999), circuit development (Rakic, 1974), molecular cues underlying development (Nakamoto et al, 1996), single-cell sequencing (Peng et al, 2019), and recent advances in computational modeling (Yamins et al, 2014). However, regarding working in a field that already possessed a "staggering mass of literature," in the 1920s Selig Hecht wrote that it was "with much trepidation" that he would write any scientific article about the visual system at all, going so far as to say that his hope was "not to add to the existing material, but rather to subtract from it" (Hecht, 1924).…”

scAAVengr: Single-cell transcriptome-based quantification of engineered AAVs in non-human primate retina

“…Scanpy (21) was used in conjunction with the Leiden clustering algorithm to assign individual cells to clusters. The hypergeometric test was then used to quantify the significance of intersection of a clusters' differentially expressed genes with retinal cell type marker genes identified previously (22,23). Each cluster was assigned a cell identity based on the most significant intersection.…”